Franz Halberg, Associate Fellow
Germaine Cornélisson, Co-Principal Investigator

Chronobiologic Assessment of Physiologic Chronomes From Womb to Tomb

Least-squares fit of harmonics, separately to 3-hourly values of each calendar year, using steps equal in frequency between 10 cycles/year and one cycle per 70 hours (A=average amplitude). The spectrum of the global planetary index of geomagnetic activity, Kp (index of disturbance of the horizontal component of the geomagnetic field), available at three-hour intervals for 59 years (1932–1990), reveals, with the approximately 27-day solar rotation component, a high harmonic content. This includes an approximately weekly component with a period of 6.74 days, a statistically-significant difference from exactly 7 days.

Strokes and other adverse vascular events are major cripplers, costing the United States an estimated yearly cost of over $30 billion. These researchers developed a system for the chronobiologic analysis of cardiovascular records with a focus on disease prevention. Ambulatory devices are now used in different geographic locations for the automatic monitoring of blood pressure and the electrocardiogram (ECG) for seven days at the outset. Chronobiologic analyses of such records serve first and foremost to improve screening, diagnosis, and treatment. From a basic viewpoint, they also serve to assess how environmental factors affect human physiology, notably heart rate, and blood pressure. The pursuit of these goals was greatly facilitated by access to the supercomputing resources, in order to:

• Analyze beat-to-beat records for resolving chronobiologic and chaotic endpoints (a typical record consists of about 2,400,000 data resampled as 0.25 second intervals over seven days)
• Automatically update reference standards as added data accumulate
• Detect the earliest risk by means of chronome alterations
• Follow up on at-risk individuals longitudinally by means of control charts

Partial spectra of data from a stand-alone magnetometer residing within the British Antarctic Survey Automated Geophysical Observatory A80. The records represent geomagnetic pulsations sampled at 0.5-second intervals from Jan. 1, 1997 to Jan 31, 1999, in an isolated area 600 km from the nearest human habitation. The three spectra correspond to the three coordinates of dB/dt (in nT/s). They were obtained on the daily mean values of 1-min standard deviations of the original 0.5-second data, analyzed over a 25-month span. Two distinct spectral peaks are observed, corresponding to signals validated by nonlinear least squares, one with a period of exactly 7 days, the other—slightly more prominent—with a period of about 6.8 days, similar to that characterizing Kp. Whereas the latter likely represents the natural component, the former may be indicative of human pollution. Components of approximately seven days are often encountered in biology. Their period was found to be inherited in studies of twin neonates by intra-class correlation analyses. This biological week is important for the patterning in time of treatment, as shown already in the case of cancer chronotherapy

A chronotherapeutic trial was also pursued to optimize the timing of treatment of blood pressure disorders.

Toward this goal, several new programs were developed, and these and existing programs were routinely applied for data analysis as they accumulate. Existing records were organized into databases so that reference values could be regularly updated and any abnormality easily detected. A library of programs for such chronobiologic applications was organized and integrated with the incorporation of graphic displays of the results.

A reduced heart rate variability and an excessive circadian blood pressure amplitude (circadian hyper-amplitude-tension: CHAT) were identified as risk factors by these researchers, and have since been documented as largely independent, both contributing additively to the risk of adverse vascular events.

Environmental effects on heart rate variability and other aspects of human physiology are slowly being recognized, with new confirmation from seven-day ECG records obtained above the Arctic Circle. The phase relation within the solar activity cycle shows a sequence of events that makes physiological sense. Cross-spectral techniques relating the biological information to physical records (also available at short intervals for very long spans, some covering several hundred years) thus gain in interest from a basic viewpoint as well.

Research Group

Miguel A. Revilla, Departamento de Matematica Apicada y Computacion, Facultad de Ciencias, Universidad de Valladolid, Valladolid, Spain